Sjogren's Syndrome (SS) is a progressive autoimmune disease affecting about 4 million Americans. The disease results in the irreversible salivary and lacrimal gland tissue damage and loss of saliva and tear production, leading to significant reduction in the quality of life in these patients. This complex disease is currently poorly understood and has no effective therapy. Diagnosis of the disease is severely hampered by the current lack of early detection and diagnostic biomarkers. Identification of biomarkers that can lead to earlier diagnosis of SS or predict the onset of the disease is critical to improve treatment and prognosis of the patients. It is in this spirit that this application is highly responsive to this RFA in that it proposes to test the hypothesis that there are proteomic and genomic signatures in the biofluid, saliva, that is produced by the major salivary glands of primary Sjogren's Syndrome (pSS) patients. This proposal aims to test the hypothesis that there are signature proteomic and genomic biomarkers in saliva of primary Sjogren's Syndrome patients that can be used for detection, and eventually early detection, of this disease in a totally non-invasive biofluid, saliva. Since there is uncertainty as to the role of ethnicity in this disease and the need to obtain homogenous patients, three specific aims are in place to test the hypothesis. Aim 1 is to engage state of the art proteome- and genome-wide discovery platforms to harness candidate biomarkers in saliva of Caucasian pSS patients. Aim 2 is to validate, train and building saliva molecular prediction models for Caucasian pSS patients. Aim 3 is to test the validated Caucasian saliva pSS molecular signature in independent cohorts of different ethnic group (Asian, Hispanic and Caucasian) available from the UCSF- Sjogren International Collaborative Clinical Alliance (SICCA). This is a timely and highly relevant research topic in the context of the intense national momentum on saliva diagnostics. The availability of robust and informative salivary biomarkers for pSS patients will positively impact the early detection, treatment decision and monitoring of this progressive autoimmune disease which affect predominately women. Our research infrastructure in salivary diagnostics technologies, proteomics and genomics technologies allow us to present this highly responsive application. For public: This research project will lead to the discovery, validation and clinical usage of saliva biomarkers can be used for early detection of patients that are susceptible to the debilitating autoimmune disease Sjogren's Syndrome, affecting up to 4 Americans each year, predominately women (9:1).